There are numerous reports relating to transition metal complexes that are used for asymmetric synthesis, including hydrogenations, transfer hydrogenations, isomerizations, oxidations, hydrosilylations, hydroborations, coupling reactions, amongst others. The reactions are usually mediated by transition metal complexes in which metals such as ruthenium, rhodium, iridium, palladium, etc. are coordinated with a tertiary phosphine compound as a catalyst.
Numerous chiral diphosphine compounds having various structures have been developed. These include Binap (R. Noyori et al. Acc. Chem. Res. 1990, 23(10), 345-350), Duphos and BPE (M. J. Burk et al. Organometallics 1990, 9(10), 2653-2655), Segphos (T. Saito et al. Adv. Synth. Catal. 2001, 343(3), 264-267), Biphemp (B. Heiser et al. Tetrahedron: Asymmetry 1991, 2(1), 51-62), Hexaphemp (J. P. Henschke et al. Adv. Synth. Catal. 2003, 345(1+2), 300-307), P-Phos (A. S. C. Chan et al. J. Am. Chem. Soc. 2000, 122(46), 11413-11514), MeO-Biphep (R. Schmid et al. Helv. Chim. Acta 1991, 74(2), 370-389), among others. In the subclass of biaryl diphosphine ligands, it has been shown that incorporation of small substituents such as methyl and methoxy groups at the b- and 6′-positions confer atropisomerism. Variations of these biaryl diphosphines containing alkoxy substituents include (R)- and (S)-(6,6′-dimethoxy(1,1-diphenyl)-2,2′-diyl)bis(diarylphosphine), or (R)- and (S)-(5,5′,6,6′-tetramethoxy(1,1′-diphenyl)-2,2′-diyl)bis(diarylphosphine), or (R)- and (S)-(4,4′,5,5′,6,6′-hexamethoxy(1,1′-diphenyl)-2,2′-diyl)bis(diarylphosphine) (R. Schmid et al. Helv. Chim. Acta 1991, 74(2), 370-389).
The preparation of the biaryl diphosphine ligands of the prior art are based on copper catalyzed Ullmann coupling of holophosphonate intermediates of formulae II, III and IV, which were subsequently reduced to the respective biaryl diphospines (R. Schmid et al. Helv. Chim. Acta 1991, 74(2), 370-389).
Intermediates II, III and IV were prepared by the ortholithiation of precursors of formulae V, VI and VII followed by halogenation with molecular I2, Br2, ICl or IBr (R. Schmid et al. Helv. Chim. Acta 1991, 74(2), 370-389).

For applications in industrial asymmetric catalysis, a metal catalyst comprising a transition metal complex of a chiral ligand must exhibit high activity and enantioselectivity for the desired transformation of a particular substrate. It is also equally important that the chiral ligand and its precursors can be prepared efficiently by an optimized synthetic route that is also amenable to scale-up. Although a very large number of chiral diphosphine ligands have been prepared in research quantities, only relatively few have been developed commercially. Hence, synthetic accessibility can often be the limiting factor for various diphosphine ligands reported in the literature.